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Biomedical subjects

E D Kilbourne

Publications and source records attributed to E D Kilbourne.

At least 55 records · Page 3Linked to original sources
PubMed1983

Monoclonal antibodies to the hemagglutinin Sa antigenic site of a/pr/8/34 influenza virus distinguish biologic mutants of swine influenza virus.

The dimorphic L and H hemagglutinin mutants of A/NJ/11/76(H1N1) (swine) influenza virus differ pleiotropically in their replication and virulence characteristics and in their antigenicity. L mutants replicate less well in chicken embryos and Madin-Darby canine kidney cells and are more infective for swine than are H mutants. L and H mutants are not antigenically distinguishable in cross-neutralization tests with homotypic antisera, but they can be identified with certain heterotypic heterogeneous antisera. The present studies demonstrate that two monoclonal antibodies (Sa-5 and Sa-13) to the Sa antigenic site of the hemagglutinin of A/PR/8/34H1N1 influenza virus react with mutants and viral reassortants containing the H hemagglutinin in radioimmunoassay, neutralization, and hemagglutination-inhibition tests but to a lesser degree or not at all with L mutants and reassortants. Conversely, monoclonal antibody (9C8) to the L mutant does not react with H mutants. L to H and H to L revertants, whether or not selected with monoclonal antibody, demonstrate concomitant change in biological and antigenic phenotype. Reactivity of H mutants with Sa monoclonal antibodies localizes the mutational site to a position on the hemagglutinin near the receptor binding site--a position in which single amino acid changes could readily influence both antigenic and biologic activity.

Antibodies, Monoclonal↗
PubMed1983

Hemagglutinin of swine influenza virus: a single amino acid change pleiotropically affects viral antigenicity and replication.

The complete nucleotide sequence has been obtained of the H1 hemagglutinin (HA) gene of a high-yielding (H) mutant of the A/NJ/11/76(H1N1) strain of swine influenza virus in studies of a viral reassortant (X-53a) bearing this gene. This determination has permitted comparison with human influenza H1N1 prototype viruses A/WSN/33 and A/PR/8/34, with which 80% and 94% amino acid homology was found between HA1 and HA2, respectively. Partial sequences have been determined for other viral reassortants containing either H or L (low-yielding phenotype) genes derived from A/NJ/11/76. Sequence of the HA1 region of an L mutant prototype was virtually completed and differed from that of the H mutant by only four amino acid changes. Sequence analysis of four other viruses was restricted to regions of the HA with which monoclonal antibodies capable of distinguishing L and H mutants are presumed to react. Therefore, changes in these sequences are relevant to changes in viral phenotype. Change at residue 155 from Gly to Glu is associated with change from L to H HA phenotype. This site, structurally equivalent to amino acid 158 on the Wiley et al. HA model [Wiley, D. C., Wilson, I. A. & Skehel, J. J. (1981) Nature (London) 289, 373-378] is near the tip of the HA monomer adjacent to the proposed receptor binding site and therefore credibly could influence both viral antigenicity and replication. Because both L and H variants exist in nature and because revertants may be selected in the laboratory as replication variants in the absence of immunoselection, these studies provide evidence for fortuitous antigenic change in association with change in biological function, which is determined by a single base change.

Antigens, Viral↗
PubMed1982

Detection of influenza virus neuraminidase-specific antibodies by an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay was developed for the titration of antibodies in human sera to influenza virus neuraminidase, employing partially purified N1 neuraminidase. Specificity of the test was demonstrated, and the test was more sensitive than either the conventional neuraminidase inhibition or plaque size reduction tests in detecting anti-neuraminidase antibody.

Antibodies, Viral↗
PubMed1982

Detection of antibodies to influenza virus M protein by an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay test system was developed in which purified influenza virus M protein was used for the detection of M antibody in human sera. Antibody levels to influenza A virus M protein were monitored in sera from a vaccine study population by using an enzyme-linked immunosorbent assay technique with purified M protein as the adsorbent antigen. A 10-fold variation in titers of preexisting M antibody was observed in this population of young adults. Increases of anti-M titer of 7- to 24-fold were observed upon immunization with Formalin-inactivated vaccine or after natural infection. The antibody response to M protein was dissociated from the response to the hemagglutinin or neuraminidase antigens. The M antibody response preceded or was coincident with the antibody response to H1 hemagglutinin upon natural exposure to circulating virus.

Antibodies, Viral↗
PubMed1980

Influenza: viral determinants of the pathogenicity and epidemicity of an invariant disease of variable occurrence.

If influenza is a riddle wrapped in mystery inside an enigma, then the viral genes are the riddle, the variable surface antigens for which they code are the mystery, and the course and cause of epidemics the ultimate enigma. Paradoxically, the disease itself has remained a stable and recognizable entity through the years, whether initiated by A/PR/8/34 or A/USSR/90/77 variant viruses. Thus, evolution appears to have preserved the disease but not the virus. Among the questions before us are: (1) Have we become obsessed with differences instead of similarities, and have we overemphasized minor differences in viral (antigenic) structure as epidemic determinants? (2) To what extent do viral antigens reflect selection by population antibody? (3) To what extent is antigenic change the pleiotropic consequence of protein structural alteration for purposes other than escape from specific neutralization? These and other questions are discussed in relating viral form to function.

Animals↗
PubMed1980

Gene composition of high-yielding influenza vaccine strains obtained by recombination.

The genetic composition of 11 high-yielding recombinants of influenza virus was determined by polyacrylamide gel electrophoresis of the 32P-labeled RNAs obtained from the recombinants and their parental viruses. The high-yield recombinants that were selected for potential use as vaccine strains contained the surface hemagglutinin and neuraminidase antigens of the low-yielding parental viruses. The increased growth capacity of the recombinants is associated with the presence of genes derived from the high-yielding laboratory strain A/Puerto Rico/8/34. Although increased growth capacity in these recombinants could not be attributed to specific genes or gene combinations, all of the high-yielding recombinants examined derived the M gene from the A/Puerto Rico/8/34 parent.

Animals↗
PubMed1979

Influenza--1979.

Explore the source record for details and available documents.

Disease Outbreaks↗
PubMed1979

Hemagglutinin mutants of swine influenza virus differing in replication characteristics in their natural host.

In two mutant clones (L and H) of A/NJ/11/76 (Hsw 1N1) influenza viruses which differ slightly antigenically and markedly in replication characteristics in chicken embryos and Madin Darby canine kidney cells, these pleiotropic differences are mediated by mutation in the hemagglutinin gene (E. D. Kilbourne, Proc. Natl. Acad. Sci. U.S.A. 75:6258--6262, 1978). Experimental infection of swine with either the mutant L and H clones or recombinant viruses differing genetically only with respect to the presence of L or H hemagglutinin demonstrated greater infectivity for the natural host of viruses bearing the L hemagglutinin. Introduction of the L but not the H hemagglutinin gene into the human influenza virus A/PR/8/34 rendered it infective for swine. Both L and H variants were isolated from pigs naturally infected with contemporary swine influenza viruses when selective conditions for the suppression of the more prevalent L mutant were employed. The L and H mutants of swine influenza virus are yet another example of viral dimorphism in nature and probably are not mere artifacts of laboratory selection. In any event, the frequent apparent allelic appearance of the two forms suggests frequent mutation and/or reversion involving a point mutation in the hemagglutinin gene. The present studies demonstrate the importance of a single gene in the pathogenesis of an influenza viral infection in its natural host.

Animals↗
PubMed1978

Genetic dimorphism in influenza viruses: characterization of stably associated hemagglutinin mutants differing in antigenicity and biological properties.

Influenza virus recombinant X-53 produced for use in the 1976 National Immunization Program for swine influenza was found to comprise two types of virions differing in their antigenic, replicative, and plaque-forming characteristics. One type, characteristic of X-53 and designated "L," was relatively low-yielding in chicken embryos, produced small clear plaques in Madin-Darby dog kidney cells, and was selectively inhibited by heterotypic antibody to the A/sw/Cam/39 strain of swine influenza virus. The other, X-53a or "H," was high-yielding in chicken embryos, produced large turbid plaques in dog kidney cells, and was not inhibited by concentrations of A/sw/Cam/39 antisera inhibitory to X-53. It was shown that A/NJ/11/76 (HswN1) virus, from which X-53 was derived, and five other swine influenza virus isolates from humans and pigs were dimorphic mixtures of the two types of virus. Segregation of the hemagglutinin genes of L and H variants by further recombination demonstrated that their different properties were pleiotropic phenotypes of mutation in the hemagglutinin gene. Under selective conditions suppressive to the L mutant, mutation of cloned L to H virus was observed. This observation, as well as the apparent ubiquity of the two mutants in nature, suggests that this is another example of viral dimorphism-the stable association of two allelic mutants. Of special significance is the indication that antigenic variants may be selected by selection for properties other than antigenicity, and therefore may represent mutants with pathogenic effects determined by factors other than lesser modulation by host antibody.

Hemagglutinins, Viral↗
PubMed1976

Genetic composition of a high-yielding influenza A virus recombinant: a vaccine strain against "Swine" influenza.

Analysis of the RNA migration pattern of a high-yielding influenza virus recombinant, X-53, used in vaccine production, reveals that only the two genes coding for hemagglutinin and neuraminidase antigens were derived from the "swine" influenza virus parent. A/New Jersey/11/76, while six were acquired from the A/PR/8/34 (HON1) parent, donor of the high yield characteristic.

Antigens, Viral↗